DE1092922B - Process for the preparation of 4- (p-Amino-benzenesulfonamido) -pyrazolo [3,4-d] pyrimidines - Google Patents

Description

GERMAN

The invention relates to a process for the preparation of 4- (p-Amino-benzenesurfonamido) -pyrazolo- [3,4-d] pyrimidines of the formulas

NH-SO,

NH,

NH-SO ₉ - '

-NH,

II

NO

N 'N

wherein R represents a hydrogen atom, a lower alkyl radical, a cycloalkyl radical or a phenyl radical and R ₁ and R _{2 represent} hydrogen atoms or lower alkyl radicals, and their salts, such as. B. the alkali or alkaline earth metal salts.

Lower alkyl radicals are z. B. the methyl radical, straight or branched propyl, butyl or amyl radicals; Cycloalkyl radicals are z. B. the cyclopentyl or the cyclohexyl radical.

In particular, the invention relates to a process for the preparation of compounds of the formula

-NH,

NH-
t
\ N
I. SO ₂ - ^ ' Ν ' N

Method of manufacture

of 4- (p-Amino-benzenesulfonamido) -

pyrazolo [3,4-d] pyrimidines

Applicant:
CIBA Aktiengesellschaft, Basel (Switzerland)

Representative: Dipl.-Ing. E. Splanemann, patent attorney,
Hamburg 36, Neuer Wall 10

Claimed priority:
Switzerland from November 27, 1957

Dr. Jean Druey, Riehen,

Dr. Paul Schmidt, Therwil,

Dr. Kurt Eichenberger and Dx. Max Wilhelm,

Basel, Switzerland),
have been named as inventors

The 1-isopropyl- - (p - amino - benzenesulfonamido) - pyrazole [3,4 - d] pyrimidine and its salts, e.g. B. the sodium salt. This Sulfonamide shows opposite with Staphyloc. aureus, Streptoc. hamm or past. avic. infected mice better healing effect than the well-known 4-p-amino-benzenesulfonamido-2,6-dimethyl-pyrimidine.

The new sulfonamides are obtained in a known manner by either

a) sulfonic acid halides of the formula

> - SO ₂ HaI

40

wherein R is a hydrogen atom, a phenyl or cycloalkyl radical, but preferably a lower alkyl radical means, and their salts as well as of the corresponding 4 - (p - Amino - benzenesulfonamido) - pyrazolo [3,4 - d] pyrimidines, which are substituted by the radical R in the 2-position.

The new compounds have in experimentally infected animals such. B. with Streptoc. haem. infected mice, a surprisingly good, protracted healing effect. They can therefore be used as a remedy for infectious diseases, z. B. in streptococcal or staphylococcal infections, use.

wherein Z denotes an amino group or a substituent which can be converted into this and Hal denotes a Halogen atom, in particular a chlorine or bromine atom, stands with pyrazolo [3,4-d] pyrimidines of formula

NH ₉

NH

R ₁

or

Λ / \,
NN

implements or

009 648/395

b) sulfonamides of the formula

SO ₂ NH ₂

with pyrazolo [3,4-d] pyrimidines of the formula

Shark

Shark

or

NO

N N

implements

30 g of p-acetylamino-benzenesulfonic acid chloride were added over a period of 25 minutes. After the exothermic reaction has subsided, the mixture is heated to 95 ° (internal temperature) for 1 hour and the reaction solution is brought to 500 cm ^{3 of} 2N hydrochloric acid and a little ice. A precipitate separates out and is filtered off with suction.

The crude product obtained in this way is ^{treated directly with 500 cm 3 of} 2.5N sodium hydroxide solution, and the suspension obtained is boiled for 2 hours, mixed with animal charcoal and

ίο filtered. The filtrate is then made up with 5N hydrochloric acid the pH value 5 to 6, after which a crystalline precipitate separates out, which is suction filtered and recrystallized from alcohol will. 1-Isopropyl-4- (p-aminobenzenesulfonamido) -pyrazolo [3,4-d] pyrimidine of the formula

NH-:

and, if appropriate, in compounds obtained converting a radical Z which can be converted into the amino group into the amino group in a manner known per se and / or obtained compounds which on a nitrogen atom are replaced by a further radical of the formula

-NH ₉

N N

are substituted, treated with hydrolyzing or aminolyzing agents and optionally obtained Compounds of the formulas I and II into their salts or the salts obtained into the compounds of the formulas I and II transferred. 3 <>

Procedures a) and b) are expediently carried out in the presence of diluents and condensation agents. One that can be converted into the amino group Substituent is e.g. B. one which is obtained by hydrolysis, such as an acylamino group, e.g. B. the acetylamino or carbethoxyamino group, by reduction, such as a nitro or azo group, or by treatment with ammonia, like a halogen atom, can be converted into the amino group.

The implementation of sulfonamides with 4-halopyrazolo [3,4-d] pyrimidines is preferably used in the presence of basic condensing agents, in particular those capable of forming salts with the sulfonamide are carried out. The sulfonamide can also be used directly in Form of a metal salt can be used. 4- (p-Z-Benzolsulfonamido) -pyrazolo are formed in the process according to the implementation [3,4-d] pyrimidines attached to a nitrogen atom by another radical of the formula

SO ₈ -

are substituted, so this can be by hydrolysis or aminolysis, for. B. by implementation with a 4-Amino-pyrazolo [3,4-d] pyrimidine of those given above Formulas, split off. The hydrolysis can be carried out at the same time as the hydrolysis of the radical Z which may be necessary Amino group can be accomplished.

Of the new 4- (p-Amino-benzenesulfonamido) -pyrazolo [3,4-d] pyrimidines can be obtained in the usual way salts, such. B. by reacting with bases, such as Alkali or alkaline earth hydroxides or organic bases.

The starting materials are known or can be obtained by methods known per se.

The invention is described in more detail in the examples below. The temperatures are in degrees Celsius specified.

example 1

A solution of 17.7 g of 1-isopropyl-4-aminopyrazolo [3,4-d] pyrimidine in 80 cm ^{3 of} pyridine becomes within CH (CH ₃ ) ₂

is thus obtained in white crystals; F. 249 to 250 °.

The 1-isopropyl-4-aminopyrazolo used as the starting material [3,4-d] pyrimidine can be obtained as follows:

8.2 g of isopropylhydrazine are placed in a solution of 16.9 g of ethoxymethylene cyanoacetate in 100 cm ^{3 of} alcohol and heated to the boil for 12 hours. It is then evaporated to dryness in vacuo and the residue is distilled in vacuo. 2-Isopropyl-3-amino-4-carbethoxy-pyrazole of the formula

C ₂ H ₅ OOC-

EUN

CH
CH ₃ CH ₃

goes over at a pressure of 10 mm Hg column at 164 to 166 ° and solidifies in crystalline form in the original. The so colorless crystals obtained melt from 46 to 48 °. 19.7 g of 2-isopropyl-4-carbethoxy-3-aminopyrazole are heated with 50 g of formamide for 4 hours in a bath from 200 to 210 °. After cooling down, you take the reaction mixture is treated in 2N sodium hydroxide solution with animal charcoal and precipitates by adjusting the pn value to 3 with 2N hydrochloric acid. 1-isopropyl-4-hydroxypyrazolo [3,4-d] pyrimidine of the formula

OH

N N

CH
CH ₃ CH ₃

is thus obtained in crystals; 197-198 °.

7.3 g of 1-isopropyl-4-hydroxypyrazolo [3,4-d] pyrimidine are ^{heated to boiling with 40 cm 3 of} phosphorus oxychloride for 5 hours. The phosphorus oxychloride is evaporated,

Bring the residue into ice water, make up with 2N sodium hydroxide solution to pH 8 and take off with ether. The ether residue is recrystallized from petroleum ether; l-isopropyl-4-chloro-pyrazolo [3,4-d] pyrimidine is obtained in this way the formula

CH
CH ₃ CH ₃

in white crystals; F. 53 °.

9 g of l-isopropyl-4-chloro-pyrazolo [3,4-d] pyrimidine and 50 cm ^{3 of} liquid ammonia are heated together in a sealed tube at 100 ° for 5 hours. After the liquid ammonia has evaporated, a white product remains which is extracted with methylene chloride. The methylene chloride residue is recrystallized from cyclohexane. The l-isopropyl-4-aminopyrazolo [3,4-d] pyrimidine of the formula obtained in this way

NH ₉

then evaporates from the ethanol in vacuo, the ß- (Na-acetyl-Nj ^ isopropyl-hydrazino) -a-cyano-acrylic acid ^{ethyl ester-containing oily residue with 150 cm 3} normal alcoholic hydrochloric acid and refluxed for 2 hours. Then the mixture is evaporated again in vacuo, the residue is taken up in 2normaler aqueous hydrochloric acid, filtered off under suction by little undissolved material and adjusts to 9 with sodium hydroxide solution to the _pH value. 8 Now is extracted with chloroform and the chloroform residue ίο recrystallized from cyclohexane. This gives 1-isopropyl-3-amino-4-carbethoxy-pyrazole of the formula

C ₂ H ₅ OOC-

XH,

N-CH

N CH ₃

in white crystals; F. 72 to 73 °.

19.7 g of 1-isopropyl-3-amino-4-carbethoxy-pyrazole

ao are heated in 50 cm ³ formamide for 5 hours in a bath from 200 to 210 °. After cooling, the precipitated crystalline precipitate is filtered off with suction and recrystallized from boiling ethyl alcohol for purification. 2-Isopropyl-4-oxy-pyrazolo [3,4-d] pyrimidine of the formula

OH

N N

CH

CH ₃ CH ₃
forms white crystals; F. 152 to 153 °.

Example 2

A solution of 5.3 g of 2-isopropyl-4-aminopyrazolo [3,4-d] pyrimidine in 40 cm ^{3 of} pyridine is mixed with 9 g of p-acetylamino-benzenesulfonic acid chloride. The mixture is then heated to 90 ° (internal temperature) for 1 hour. The reaction solution is brought to 300 cm ^{3 of} 2N hydrochloric acid and a little ice. A precipitate separates out and is filtered off with suction.

^{100 cm 3 of} 2.5N sodium hydroxide solution are added directly to the crude product obtained in this way, and the suspension obtained is boiled for 2 hours, animal charcoal is added and the mixture is filtered. The filtrate is then adjusted to pH 4 to 5 with 5N hydrochloric acid, after which a crystalline precipitate separates out and is recrystallized from alcohol. 2 - Isopropyl - 4 - (p - amino - benzenesulfonamido) - pyrazolo [3,4-d] pyrimidine of the formula

NH-SO,

> -NH ₂

N-CH (CH ₃ ),

N N

.CH,

N-CH

N N

CH,

is thus obtained in crystals; F. 229 to 230 °.

10 g of 2-isopropyl-4-oxy-pyrazolo [3,4-d] pyrimidine and 15 g of phosphorus pentasulfide are placed in 100 cm ^{3 of} pyridine; the mixture is then heated in a bath of 130 ° for 4 hours. The hot pyridine solution is then poured into 1000 cm ^{3 of} water, after which a brown precipitate separates out on standing. The latter is dissolved in dilute sodium hydroxide solution, treated with animal charcoal, precipitated using dilute hydrochloric acid and, after recrystallization from ethanol, 2-isopropyl-4-mercapto-pyrazolo [3,4-d] pvrimidine of the formula is obtained

SH

CH,

N-CH

N N

CH,

in crystals; F. 237 to 239 °.

19.4 g of 2-isopropyl-4-mercapto-pyrazolo [3,4-d] pyrimidine are placed in 150 cm ^{3 of} 1 η-sodium hydroxide solution. The solution is slowly mixed with 16 g of dimethyl sulfate while stirring and then stirred for a further 30 minutes at room temperature. The precipitate is then filtered off with suction and recrystallized from ethanol. 2-Isopropyl-4-thio-5-methyl-4,5-dihydropyrazolo [3,4-d] pyrimidine of the formula

H, C -N

τ , CHo

N-CH

is thus obtained in white crystals; F. 225 to 227 °.

The 2-isopropyl-4-aminopyrazolo [3,4-d] pyrimidine used as starting material can be obtained as follows:

A solution of 11.6 g of isopropyl-N ^ acetyl-hydrazine and 17 g of ethoxymethylene cyanoacetic ester in 250 cm ^{3 of} ethanol is refluxed for 12 hours. One 70 is thus obtained in crystals; F. 178 to 180 °.

N N

CH,

The alkaline, aqueous filtrate is then extracted with a large amount of chloroform and obtained after evaporation of the chloroform as residue yellow crystals, which are recrystallized from a little isopropyl ether. 2-isopropyl-4-methylmercapto-pyrazolo [3,4-d] pyrimidine the formula vacuum. 2 ~ (sec-butyl) -3-amino-4-carbethoxy-pyrazole of the formula

C ₂ H ₅ OOC-

H ₉ N-

NS,

Ί / N-CH

CH,

"CH,

is thus obtained in white crystals; F. 78 to 79 °.

8.5 g of 2-isopropyl-4-methylmercapto-pyrazolo [3,4-d] -pyrimidine are ^{heated together with 80 cm 3 of} liquid ammonia in the autoclave to 95 ° to 100 ° for 20 hours. The residue is dissolved in 20 cm ³ of 1N hydrochloric acid, a little undissolved material is then filtered off with suction and the filtrate is treated with 10N sodium hydroxide solution, a solid precipitate separating out. This is recrystallized from ethanol and 2-isopropyl-4-aminopyrazolo [3,4-d] pyrimidine of the formula CH CH ₃ C ₂ H _{6 is obtained}

boils at a pressure of 0.09 mm Hg column at 105 to 107 °.

10.4 g of 2- (sec-butyl) -3-amino-4-carbethoxy-pyrazole are heated with 25 cm ^{3 of} formamide at 200 to 210 ° for 6 hours. The crystalline 1- (sec-butyl) -4-hydroxypyrazolo [3,4-d] pyrimidine of the formula OH is obtained from the reaction solution cooled to a temperature of 0 °

/
N

NH,

N N

CH, CH

N-CH

NN

CH ₃

in white crystals; F. 236 to 237 °.

Example 3

A solution of 9.55 g l-sec-Butyl-4-amino-pyrazolo [3,4-d] pyrimidine in 50 cm ³ of absolute pyridine is within 30 minutes with 13.35 g of 96 ° / ₀ sodium p- Acetylamino-benzenesulfonic acid chloride added. After the exothermic reaction has subsided, the mixture is heated to 95 ° (internal temperature) for 1 hour and then evaporated in vacuo. The residue thus obtained is directly related to 150 cm ³ were added 2N sodium hydroxide solution, and the resulting suspension is boiled for 2 ¹ J ₂ hours under reflux, treated with charcoal and filtered. It then provides to the filtrate 5N hydrochloric acid to the _pH value 5 a, after which a crystalline precipitate is filtered off with suction and recrystallized from ethanol precipitated. The 1-sec-butyl-4- (p-amino-benzenesulfonamido) -pyrazolo [3,4-d] pyrimidine of the formula is obtained in this way

F. 174 to 175 °.

9.6 g of l- (sec-butyl) -4-hydroxypyrazolo [3,4-d] pyrimidine are ^{refluxed with 50 cm 3 of} phosphorus oxychloride for 8 hours. The phosphorus oxychloride is evaporated off, the residue is placed in ice water, adjusted to a pn value of 10 with 2N sodium hydroxide solution, extracted with ether and the ether residue is distilled in vacuo. 1 - (sec - butyl) - 4 - chloro - pyrazolo [3,4 - d] pyrimidine of the formula

Cl

ι

NH-SO ₃

; --NH,

CH

CH

CH ₃ C ₂ H ₅

boils at 137 to 138 ° at a pressure of 10 mm Hg column.

11.4 g of l-sec-butyl-4-chloro-pyrazolo [3,4-d] pyrimidine are ^{heated in 250 cm 3 of} normal alcoholic ammonia for 5 hours to 140 ° to 150 °. After cooling, the reaction solution is evaporated to dryness, the residue is mixed with water and extracted with methylene chloride. After evaporating the methylene chloride solution, the residue obtained is l-sec-butyl-4-aminopyrazolo [3,4-d] pyrimidine of the formula NH,

F. 225 to 226 °.

The 1-sec-butyl-4-aminopyrazolo [3,4-d] pyrimidine used as starting material can be obtained as follows:

16.9 g of ethyl ethoxymethylene cyanoacetate and 8.8 g of sec-butyl hydrazine are ^{heated to boiling in 100 cm 3 of} absolute ethanol for 10 hours. It is then evaporated in vacuo and the residue is distilled in

N N

CH

/ \
CH ₃ C ₂ H ₆

F. 128 to 130 °. After recrystallizing once from ether, the melting point rises to 131 to 132 °.

Example 4

A solution of 10.15 g of l-cyclopentyl-4-amincpyrazolo [3,4-d] pyrimidine in 50 cm ³ of pyridine inneihalb of 30 minutes with 13.35 g of 92.5 ° / ₀ sodium p-Acetylaminobenzolsulfochlorid is added. After the exothermic reaction has subsided, the mixture is heated to 90 ° (internal temperature) for 1 hour and then evaporated in vacuo. The residue thus obtained is directly related to 150 cm ³ were added 2N sodium hydroxide solution, and the resulting suspension is boiled for 2 ¹ J ₂ hours under reflux. During this hydrolysis, the bis-p-aminobenzenesulfonamide compounds formed are also converted into the desired mono derivatives. After completion of hydrolysis is treated with animal charcoal, filtered and the filtrate is treated with 5N hydrochloric acid to the _pH value 5, whereupon an oily precipitate separates out. The supernatant aqueous solution is then decanted, the oily portion is taken up again in 100 cm ^{3 of} 2N sodium hydroxide solution, filtered and the filtrate is adjusted to pn value 4 with 5N hydrochloric acid, whereupon a viscous paste separates. The supernatant aqueous solution is poured off and the viscous paste is recrystallized from ethanol. This gives 1-cyclopentyl-4- (p-aminobenzenesulfonamido) pyrazolo [3,4-d] pyrimidine of the formula

pyrazole of the formula

NC

H ₉ N -

precipitates in crystals; 110 to 112 degrees. After recrystallizing once from 40 ° / ₀ strength aqueous ethanol, the melting point rises to 113 ° to 114 °.

20 g of 2-cyclopentyl-3-amino-4-cyano-pyrazole are heated in 60 cm ^{3 of} formamide to 200 to 210 ° for 8 hours. After cooling, the reaction mixture is mixed with water and extracted with methylene chloride. The residue obtained from the methylene chloride ^{solution is dissolved in 80 cm 3 of} 1 η-hydrochloric acid, filtered with charcoal and the filtrate is adjusted to a pn value of 7 with 2N sodium hydroxide solution, whereupon crude 1-cyclopentyl-4-aminopyrazolo [3, 4-d] pyrimidine of the formula
NH ₅ ,

N N

NH-SO,

NH,

35 separates, F. 145 to 146 °, which is directly for the
described implementation can be used.

Example 5

F. 249 to 250 °.

The 1-cyclopentyl-4-aminopyrazolo [3,4-d] pyrimidine used as starting material can be obtained as follows:

A solution of 200 g of hydrazine hydrate in 572 cm ^{3 of} 7N hydrochloric acid is admixed with 336 g of cyclopentanone while stirring and cooling with ice. It is then hydrogenated at room temperature and a pressure of 100 atmospheres with 2 g of platinum oxide as a catalyst. The amount of hydrogen calculated for 4MoI, 89.61, is absorbed within 1 hour. The catalyst is filtered off with suction, the filtrate is adjusted to pH 4 with 2N hydrochloric acid and the solution is concentrated in vacuo until crystallization begins. 500 cm ^{3 of} concentrated sodium hydroxide solution are then added while cooling with ice. Solid sodium hydroxide is still added until the cyclopentylhydrazine separates out as an oil. The latter distilled over at a pressure of 11 mm Hg column at 60 to 65 °.

48.8 g of ethoxymethylene malonic acid dinitrile are dissolved in 320 cm ^{3 of} ethyl alcohol and a solution of 40 g of freshly distilled cyclopentylhydrazine in 80 cm ^{3 of} ethanol is added. It is heated to the boil for 10 hours. The ethyl alcohol is evaporated off in vacuo, a solid product precipitating out. The residue is dissolved in 80 cm ^{3 of} ethyl alcohol and 500 cm ^{3 of} water are added while stirring, the 2-CycIopentyl-3-amino-4-cyano-A solution of 10.85 g of 1-cyclohexyl-4-amino-pyrazolo [3 , 4-d] pyrimidine in 50 cm ^{3 of} absolute pyridine is admixed with 13.9 g of 92.5% p-acetylaminobenzenesulphonic acid chloride in the course of 30 minutes. After the exothermic reaction has subsided, the mixture is heated to 90 to 95 ° (internal temperature) for 1 hour and then evaporated in vacuo. The residue thus obtained is mixed ³ 2 η sodium hydroxide solution directly to 150 cm and the resulting suspension l ^x / boiled for ₂ hours under reflux, treated with charcoal and filtered. The filtrate is then adjusted to pH 4 with 5η hydrochloric acid, whereupon an oily precipitate separates out. The supernatant water is then poured off, and 100 cm ^{3 of} 2 η sodium hydroxide solution are added to the oily precipitate. The portion of the oil which is insoluble in sodium hydroxide solution is discarded, the aqueous alkaline solution is adjusted to pH 4 with 5η hydrochloric acid, after which a crystalline precipitate separates out. This precipitate is recrystallized from ethanol. 1-Cyclohexyl 4- (p-amino-benzenesulfonamido) -pyrazolo [3,4-d] pyrimidine of the formula is obtained in this way

NH

NH,

60

N N

H !

F. 246 to 247 °.

009 648/395

C ₂ H ₆ OOC
H ₂ N-

H !

112 to 114 degrees. When recrystallizing from petroleum ether, the melting point rises to 115 ° to 116 °.

20 g of 2 ~ cyclohexyl-3-amino-4-carbethoxy-pyrazole become heated with 50 g of formamide for 6 hours in a bath from 200 to 210 °. After cooling, it crystallizes 1 -Cyclohexyl-4-hydroxy-pyrazolo [3,4-d] pyrimidine of the formula

OH

The 1-cyclohexyl-4-aminopyrazolo [3,4-d] pyrimidine used as starting material is made as follows:

A solution of 200 g of hydrazine hydrate in 572 cm ^{3 of} 7N hydrochloric acid is admixed with 392 g of cyclohexanone while stirring and cooling with ice. It is then hydrogenated at room temperature and a pressure of 100 atmospheres with 2 g of platinum oxide as a catalyst. The amount of hydrogen calculated for 4MoI, 89.61, is absorbed within 30 minutes. 1000 cm ^{3 of} ethyl alcohol are then added in order to dissolve the precipitated crystals. The catalyst is then filtered off with suction, the filtrate is adjusted to pH 4 and concentrated in vacuo until crystallization begins. After cooling, the precipitated crystals are filtered off, and 500 cm ^{3 of} concentrated sodium hydroxide solution are added to the filtrate while cooling with ice. Solid sodium hydroxide is still added until the cyclohexylhydrazine separates out as an oil. The latter distills at a pressure of 12 mm Hg column at 77 to 80 °. The distillate obtained is immediately converted into the hydrochloride with alcoholic hydrochloric acid; 112 to 113 °.

A solution of 2.3 g of sodium in 40 cm ^{3 of} absolute ethanol is added to a solution of 15.05 g of cyclohexylhydrazine hydrochloride in 50 cm ^{3 of absolute ethanol.} This reaction solution is mixed with 16.9 g of ethyl ethoxymethylene cyanoacetate, dissolved in 20 cm ^{3 of} ethanol, and heated to the boil for 10 hours. After cooling, the precipitated sodium chloride is filtered off with suction and the filtrate is evaporated to dryness. The crystalline residue is triturated with water and suction filtered. This gives 2-cyclohexyl-3-amino-4-carbethoxy-pyrazole of the formula

recrystallized. 1-Cyclohexyl-4-chloropyrazo] o [3,4-d] pyrimidine is obtained in this way the formula

Cl

N N

in white crystals; F. 67 to 68 °.

11.83 g of 1-cyclohexyl-4-chloro-pyrazolo [3,4-d] pyrimidine are ^{heated with 120 cm 3 of} 8 normal alcoholic ammonia solution in a closed tube at 140 ° to 150 ° for 5 hours. After the reaction solution has been evaporated, water is added to the residue and the mixture is extracted with methylene chloride. The residue obtained from the evaporated methylene chloride solution is 1-cyclohexyl-4-aminopyrazolo [3,4-d] pyrimidine of the formula

NH ₂

35

188 to 189 °.

Example 6

A solution of 10.25 g of l-pentyl- (3 ') -4-aminopyrazolo [3,4-d] pyrimidine in 50 cm ^{3 of} pyridine is mixed with 13.9 g of 92.5% p -Acetylaminobenzolsulfonsäurechlorid added. After the reaction has subsided, the mixture is heated to 90 ° (internal temperature) for 1 hour and then evaporated in vacuo. ^{150 cm 3 of} 2N sodium hydroxide solution are added directly to the residue obtained in this way, and the suspension obtained is ^{refluxed 2 ×} / ₂ hours, animal charcoal is added and the mixture is filtered. It then sets the filtrate with 5 η-hydrochloric acid to the _pH value 4, whereupon an oily

Precipitation separates. The supernatant aqueous solution is decanted and dissolves the residual oil in 200 cm ³ 1 η-sodium hydroxide solution, the solution is filtered and, with 5 η hydrochloric acid back to the _pH value 4, a, after which time a crystalline precipitate separates out, the off

sucked and is recrystallized from ethanol. 1-pentyl (3 ') -4- (p-Amino-benzenesulfonamido) pyrazolo [3,4-d] pyrimidine the formula

NH

-NH,

60

the end. It shows a melting point of 245 to 246 °.

21.8 g of 1 - cyclohexyl - 4 - hydroxypyrazolo [3,4 - d] pyr - 65 imidine are ^{heated to boiling with 100 cm 3 of} phosphorus oxychloride for 8 hours. The phosphorus oxychloride is evaporated off, the residue is brought into ice water, adjusted to a pn value of 10 with 2η sodium hydroxide solution and extracted with ether. The ether residue is obtained from petroleum ether 70 as white crystals; 192 to 192.5 degrees.

CH

C, H.

C ₂ H ₅

The 1-pentyl- (3 ') -4-aminopyrazolo [3,4-d] pyrimidine used as starting material is made as follows:

A solution of 200 g of hydrazine hydrate in 528 cm ^{3 of} 7.57 η hydrochloric acid is mixed with 344 g of diethyl ketone while stirring and cooling with ice. After adding 270 cm ^{3 of} ethanol, the mixture is stirred for a further 30 minutes. It is then hydrogenated at room temperature and a pressure of 130 atmospheres with 2 g of platinum oxide as a catalyst. The amount of hydrogen calculated for 4 moles, 89.61, is absorbed within 15 minutes. The catalyst is filtered off with suction, the filtrate is adjusted to a pn value of 4 with 2N hydrochloric acid and the solution is concentrated in vacuo until crystallization begins. 500 cm ^{3 of} concentrated sodium hydroxide solution are then added while cooling with ice. Solid sodium hydroxide is still added until the isopentylhydrazine separates out as an oil. The oil is decanted, dried over sodium hydroxide and distilled. Pentyl-3-hydrazine distilled over between 46 and 50 ° at a pressure of 12 mm Hg column.

12.2 g of ethoxymethylene malonic acid dinitrile are dissolved in ao 200 cm ^{3 of} ethyl alcohol, and 10.1 g of pentyl-3-hydrazine are added. The mixture is heated to boiling for 12 hours. The ethyl alcohol is then evaporated in vacuo, a solid product precipitating out. The latter is recrystallized from ethyl alcohol and so is the 2-pentyl- (3 ') ~ 3-amino-4-cyano-pyrazole of the formula

NC
H ₂ N-

the 1 -methyl-4- (p-amino-benzenesulfonamido) -pyrazolo- [3,4-d] pyrimidine the formula

NH-SO,

NH ₅

N N

CH ₃
in white crystals; F. 290 to 291 °.

Claims (1)

Claim: Process for the preparation of 4- (p-Amino-benzenesulfonamido) -pyrazolo [3,4-d] pyrimidines of the formulas CH
/ \
C ₂ H ₅ C ₂ H ₈ 35 preserved in crystals; F. 140 to 141 °. 20 g of 2-pentyl- (3 ') -3-amino-4-cyano-pyrazole are heated in 60 cm ^{3 of} formamide to 200 ° to 220 ° for 8 hours. After cooling, the reaction product is mixed with water, extracted with methylene chloride and the residue obtained from the evaporated methylene chloride solution is recrystallized from ether-petroleum ether. The l-pentyl- (3 ') -4-aminopyrazolo [3,4-d] pyrimidine of the formula is obtained in this way NH N N CH
/ \
C ₂ H ₅ C ₂ H ₅ F. 146 to 147 °. 55 60 Example 7 5 g of sodium sulfanilamide and 5 g of l-methyl-4-chloropyrazolo [3,4-d] pyrimidine are refluxed for ^{6 hours in 50 cm 3 of} absolute tetrahydrofuran. The solvent is then removed in vacuo and the residue is dissolved in 20 cm ^{3 of} 2 η sodium hydroxide solution. When 20 cm ^{3 of} 2 η-hydrochloric acid are added, a white precipitate separates out and is recrystallized from ethanol. One obtains NH-SO, NH, and NH NH. wherein R represents a hydrogen atom, a lower alkyl radical, a cycloalkyl radical or a phenyl radical and R ₁ and R _{2 represent} hydrogen atoms or lower alkyl radicals, and their salts, characterized in that either a) sulfonic acid halides of the formula -SO-HaI wherein Z denotes an amino group or a substituent which can be converted into this, and Hai represents a halogen atom with pyrazolo [3,4-d] pyrimidines the formula NH. NH, or N N implements or b) sulfonamides of the formula
Z SO ₉ NH, with pyrazolo [3,4-d] pyrimidines of the formula Hal Hal or radical Z which can be converted into the amino group is converted into the amino group in a manner known per se and / or compounds obtained which are attached to a nitrogen atom by a further radical of the formula implements and possibly in the compounds obtained a • SO, - are substituted, treated with hydrolyzing or aminolyzing agents and optionally obtained Compounds of the formulas I and II into their salts or the salts obtained into the compounds of Formulas I and II transferred.